Facteurs de risque fracturaire, nouveaux traitements: comment evolue la prise en charge de l'ostéoporose de la personne agée [Fracture risk, new treatments: how does the management of the osteoporosis of elderly change?]

Osteoporosis of elderly is a growing medical, economic and health-care problem. It is due to the increase of the life expectancy and the number of osteoporotic fractures. With the new Swiss-specific tool FRAX and the development of inpatients fracture trajectory, we can better identify patients with high risk of fracture. An appropriate treatment can be proposed more quickly. The follow-up of bone markers increases the treatment efficiency. With a better identification, treatment and follow-up of osteoporosis of elderly patients, we can ameliorate the patient's quality of life and decrease the number of osteoporotic fractures with a good cost-effectiveness ratio.

Vertebral microarchitecture and fragility fracture in men: a TBS study.

INTRODUCTION: Although osteoporosis is considered a disease of women, 25% of the individuals with osteoporosis are men. BMD measurement by DXA is the gold standard used to diagnose osteoporosis and assess fracture risk. Nevertheless, BMD does not take into account alterations of microarchitecture. TBS is an index of bone microarchitecture extracted from the spine DXA. Previous studies have reported the ability of the spine TBS to predict osteoporotic fractures in women. This is the first case-controlled study in men to evaluate the potential diagnostic value of TBS as a complement to bone mineral density (BMD), by comparing men with and without fractures. METHODS: To be eligible for this study, subjects had to be non-Hispanic US white men aged 40 and older. Furthermore, subjects were excluded if they have or have had previously any treatment or illness that may influence bone metabolism. Fractured subjects were included if the presence of at least one fracture was confirmed. Cases were matched for age (±3 years) and BMD (±0.04 g/cm(2)) with three controls. BMD and TBS were first retrospectively evaluated at AP spine (L1-L4) with a Prodigy densitometer (GE-Lunar, Madison, USA) and TBS iNsight® (Med-Imaps, France) in Lausanne University Hospital blinded from clinical outcome. Inter-group comparisons were undertaken using Student's t-tests or Wilcoxon signed rank tests. Odds ratios were calculated per one standard deviation decrease as well as areas under the receiver operating curve (AUC). RESULTS: After applying inclusion/exclusion criteria, a group of 180 male subjects was obtained. This group consists of 45 fractured subjects (age=63.3±12.6 years, BMI=27.1±4.2 kg/m(2)) and 135 control subjects (age=62.9±11.9 years, BMI=26.7±3.9 kg/m(2)) matched for age (p=0.86) and BMD (p=0.20). A weak correlation was obtained between TBS and BMD and between TBS and BMI (r=0.27 and r=-0.28, respectively, p<0.01). Subjects with fracture have a significant lower TBS compared to control subjects (p=0.013), whereas no differences were obtained for BMI, height and weight (p>0.10). TBS OR per standard deviation is 1.55 [1.09-2.20] for all fracture type. When considering vertebral fracture only TBS OR reached 2.07 [1.14-3.74]. CONCLUSION: This study showed the potential use of TBS in men. TBS revealed a significant difference between fractured and age- and spine BMD-matched nonfractured subjects. These results are consistent with those previously reported on for men of other nationalities.

Official Positions for FRAX® clinical regarding international differences from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX®.

Osteoporosis is a serious worldwide epidemic. Increased risk of fractures is the hallmark of the disease and is associated with increased morbidity, mortality and economic burden. FRAX® is a web-based tool developed by the Sheffield WHO Collaborating Center team, that integrates clinical risk factors, femoral neck BMD, country specific mortality and fracture data and calculates the 10 year fracture probability in order to help health care professionals identify patients who need treatment. However, only 31 countries have a FRAX® calculator at the time paper was accepted for publication. In the absence of a FRAX® model for a particular country, it has been suggested to use a surrogate country for which the epidemiology of osteoporosis most closely approximates the index country. More specific recommendations for clinicians in these countries are not available. In North America, concerns have also been raised regarding the assumptions used to construct the US ethnic specific FRAX® calculators with respect to the correction factors applied to derive fracture probabilities in Blacks, Asians and Hispanics in comparison to Whites. In addition, questions were raised about calculating fracture risk in other ethnic groups e.g., Native Americans and First Canadians. In order to provide additional guidance to clinicians, a FRAX® International Task Force was formed to address specific questions raised by physicians in countries without FRAX® calculators and seeking to integrate FRAX® into their clinical practice. The main questions that the task force tried to answer were the following: The Task Force members conducted appropriate literature reviews and developed preliminary statements that were discussed and graded by a panel of experts at the ISCD-IOF joint conference. The statements approved by the panel of experts are discussed in the current paper.

FRAX(®) Clinical Task Force of the 2010 Joint International Society for Clinical Densitometry & International Osteoporosis Foundation Position Development Conference.

The World Health Organization fracture risk assessment tool, FRAX(®), is an advance in clinical care that can assist in clinical decision-making. However, with increasing clinical utilization, numerous questions have arisen regarding how to best estimate fracture risk in an individual patient. Recognizing the need to assist clinicians in optimal use of FRAX(®), the International Osteoporosis Foundation (IOF) in conjunction with the International Society for Clinical Densitometry (ISCD) assembled an international panel of experts that ultimately developed joint Official Positions of the ISCD and IOF advising clinicians regarding FRAX(®) usage. As part of the process, the charge of the FRAX(®) Clinical Task Force was to review and synthesize data surrounding a number of recognized clinical risk factors including rheumatoid arthritis, smoking, alcohol, prior fracture, falls, bone turnover markers and glucocorticoid use. This synthesis was presented to the expert panel and constitutes the data on which the subsequent Official Positions are predicated. A summary of the Clinical Task Force composition and charge is presented here.

Postgraduate Symposium: Positive influence of nutritional alkalinity on bone health.

There is growing evidence that consumption of a Western diet is a risk factor for osteoporosis through excess acid supply, while fruits and vegetables balance the excess acidity, mostly by providing K-rich bicarbonate-rich foods. Western diets consumed by adults generate approximately 50-100 mEq acid/d; therefore, healthy adults consuming such a diet are at risk of chronic low-grade metabolic acidosis, which worsens with age as a result of declining kidney function. Bone buffers the excess acid by delivering cations and it is considered that with time an overstimulation of this process will lead to the dissolution of the bone mineral content and hence to reduced bone mass. Intakes of K, Mg and fruit and vegetables have been associated with a higher alkaline status and a subsequent beneficial effect on bone health. In healthy male volunteers an acid-forming diet increases urinary Ca excretion by 74% and urinary C-terminal telopeptide of type I collagen (C-telopeptide) excretion by 19% when compared with an alkali (base-forming) diet. Cross-sectional studies have shown that there is a correlation between the nutritional acid load and bone health measured by bone ultrasound or dual-energy X-ray absorptiometry. Few studies have been undertaken in very elderly women (>75 years), whose osteoporosis risk is very pertinent. The EVAluation of Nutrients Intakes and Bone Ultra Sound Study has developed and validated (n 51) an FFQ for use in a very elderly Swiss population (mean age 80.4 (sd 2.99) years), which has shown intakes of key nutrients (energy, fat, carbohydrate, Ca, Mg, vitamin C, D and E) to be low in 401 subjects. A subsequent study to assess net endogenous acid production (NEAP) and bone ultrasound results in 256 women aged > or = 75 years has shown that lower NEAP (P=0.023) and higher K intake (P=0.033) are correlated with higher bone ultrasound results. High acid load may be an important additional risk factor that may be particularly relevant in very elderly patients with an already-high fracture risk. The latter study adds to knowledge by confirming a positive link between dietary alkalinity and bone health indices in the very elderly. In a further study to complement these findings it has also been shown in a group of thirty young women that in Ca sufficiency an acid Ca-rich water has no effect on bone resorption, while an alkaline bicarbonate-rich water leads to a decrease in both serum parathyroid hormone and serum C-telopeptide. Further investigations need to be undertaken to study whether these positive effects on bone loss are maintained over long-term treatment. Mineral-water consumption could be an easy and inexpensive way of helping to prevent osteoporosis and could be of major interest for long-term prevention of bone loss.

Mortality associated with diabetes mellitus in comparison with history of cardiovascular disease in older women.

BACKGROUND: Women with diabetes mellitus have an increased risk of cardiovascular disease (CVD) mortality and current treatment guidelines consider diabetes to be equivalent to existing CVD, but few data exist about the relative importance of these risk factors for total and cause-specific mortality in older women. METHODS: We studied 9704 women aged ≥65 years enrolled in a prospective cohort study (Study of Osteoporotic Fractures) during a mean follow-up of 13 years and compared all-cause, CVD and coronary heart disease (CHD) mortality among non-diabetic women without and with a prior history of CVD at baseline and diabetic women without and with a prior history of CVD. Diabetes mellitus and prior CVD (history of angina, myocardial infarction or stroke) were defined as self-report of physician diagnoses. Cause of death was adjudicated from death certificates and medical records when available (>95% deaths confirmed). Ascertainment of vital status was 99% complete. Log-rank tests for the rates of death and multivariate Cox hazard models adjusted for age, smoking, physical activity, systolic blood pressure, waist girth and education were used to compare mortality among the four groups with non-diabetic women without CVD as the referent group. Results are reported as adjusted hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: At baseline mean age was 71.7±5.3 years, 7.0% reported diabetes mellitus and 14.5% reported prior CVD. 4257 women died during follow-up, 36.6% were attributed to CVD. The incidence of CVD death per 1000 person-years was 9.9 and 21.6 among non-diabetic women without and with CVD, respectively, and 23.8 and 33.3 among diabetic women without and with CVD, respectively. Compared to nondiabetic women without prior CVD, the risk of CVD mortality was elevated among both non-diabetic women with CVD (HR=1.82, CI: 1.60-2.07, P<0.001) and diabetic women without prior CVD (HR=2.24, CI: 1.87-2.69, P<0.001). CVD mortality was highest among diabetic women with CVD (HR=3.41, CI: 2.61-4.45, P<0.001). Compared to non-diabetic women with CVD, diabetic women without prior CVD had a significantly higher adjusted HR for total and CVD mortality (P<0.001 and P<0.05 respectively). CHD mortality did not differ significantly between non-diabetic women with CVD and diabetic women without prior CVD. CONCLUSION: Older diabetic women without prior CVD have a higher risk of all-cause and CVD mortality and a similar risk of CHD mortality compared to non-diabetic women with pre-existing CVD. For older women, these data support the equivalence of prior CVD and diabetes mellitus in current guidelines for the prevention of CVD.

Evaluation of the potential use of trabecular bone score to complement bone mineral density in the diagnosis of osteoporosis: a preliminary spine BMD-matched, case-control study.

The trabecular bone score (TBS) is a new parameter that is determined from gray-level analysis of dual-energy X-ray absorptiometry (DXA) images. It relies on the mean thickness and volume fraction of trabecular bone microarchitecture. This was a preliminary case-control study to evaluate the potential diagnostic value of TBS as a complement to bone mineral density (BMD), by comparing postmenopausal women with and without fractures. The sample consisted of 45 women with osteoporotic fractures (5 hip fractures, 20 vertebral fractures, and 20 other types of fracture) and 155 women without a fracture. Stratification was performed, taking into account each type of fracture (except hip), and women with and without fractures were matched for age and spine BMD. BMD and TBS were measured at the total spine. TBS measured at the total spine revealed a significant difference between the fracture and age- and spine BMD-matched nonfracture group, when considering all types of fractures and vertebral fractures. In these cases, the diagnostic value of the combination of BMD and TBS likely will be higher compared with that of BMD alone. TBS, as evaluated from standard DXA scans directly, potentially complements BMD in the detection of osteoporotic fractures. Prospective studies are necessary to fully evaluate the potential role of TBS as a complementary risk factor for fracture.

Recommendations for raloxifene use in daily clinical practice in the Swiss setting.

BACKGROUND/AIM: Raloxifene is the first selective estrogen receptor modulator that has been approved for the treatment and prevention of osteoporosis in postmenopausal women in Europe and in the US. Although raloxifene reduces the risk of invasive breast cancer in postmenopausal women with osteoporosis and in postmenopausal women at high risk for invasive breast cancer, it is approved in that indication in the US but not in the EU. The aim was to characterize the clinical profiles of postmenopausal women expected to benefit most from therapy with raloxifene based on published scientific evidence to date. METHODS: Key individual patient characteristics relevant to the prescription of raloxifene in daily practice were defined by a board of Swiss experts in the fields of menopause and metabolic bone diseases and linked to published scientific evidence. Consensus was reached about translating these insights into daily practice. RESULTS: Through estrogen agonistic effects on bone, raloxifene reduces biochemical markers of bone turnover to premenopausal levels, increases bone mineral density (BMD) at the lumbar spine, proximal femur, and total body, and reduces vertebral fracture risk in women with osteopenia or osteoporosis with and without prevalent vertebral fracture. Through estrogen antagonistic effects on breast tissue, raloxifene reduces the risk of invasive estrogen-receptor positive breast cancer in postmenopausal women with osteoporosis and in postmenopausal women at high risk for invasive breast cancer. Finally, raloxifene increases the incidence of hot flushes, the risk of venous thromboembolic events, and the risk of fatal stroke in postmenopausal women at increased risk for coronary heart disease. Postmenopausal women in whom the use of raloxifene is considered can be categorized in a 2 × 2 matrix reflecting their bone status (osteopenic or osteoporotic based on their BMD T-score by dual energy X-ray absorptiometry) and their breast cancer risk (low or high based on the modified Gail model). Women at high risk of breast cancer should be considered for treatment with raloxifene. CONCLUSION: Postmenopausal women between 50 and 70 years of age without climacteric symptoms with either osteopenia or osteoporosis should be evaluated with regard to their breast cancer risk and considered for treatment with raloxifene within the framework of its contraindications and precautions.

Clinical factors associated with trabecular bone score.

Dual-energy X-ray absorptiometry (DXA) measurement of bone mineral density (BMD) is the reference standard for diagnosing osteoporosis but does not directly reflect deterioration in bone microarchitecture. The trabecular bone score (TBS), a novel grey-level texture measurement that can be extracted from DXA images, predicts osteoporotic fractures independent of BMD. Our aim was to identify clinical factors that are associated with baseline lumbar spine TBS. In total, 29,407 women ≥50yr at the time of baseline hip and spine DXA were identified from a database containing all clinical results for the Province of Manitoba, Canada. Lumbar spine TBS was derived for each spine DXA examination blinded to clinical parameters and outcomes. Multiple linear regression and logistic regression (lowest vs highest tertile) was used to define the sensitivity of TBS to other risk factors associated with osteoporosis. Only a small component of the TBS measurement (7-11%) could be explained from BMD measurements. In multiple linear regression and logistic regression models, reduced lumbar spine TBS was associated with recent glucocorticoid use, prior major fracture, rheumatoid arthritis, chronic obstructive pulmonary disease, high alcohol intake, and higher body mass index. In contrast, recent osteoporosis therapy was associated with a significantly lower likelihood for reduced TBS. Similar findings were seen after adjustment for lumbar spine or femoral neck BMD. In conclusion, lumbar spine TBS is strongly associated with many of the risk factors that are predictive of osteoporotic fractures. Further work is needed to determine whether lumbar spine TBS can replace some of the clinical risk factors currently used in fracture risk assessment.

Official Positions for FRAX® clinical regarding smoking from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX®.

The worldwide prevalence of smoking has been estimated at about 50% in men, and 10% in women, with larger variations among different populations studied. Smoking has been shown to affect many organ systems resulting in severe morbidity and increased mortality. In addition, smoking has been identified as a predictor of ten-year fracture risk in men and women, largely independent of an individual's bone mineral density. This finding has eventually lead to incorporation of this risk factor into FRAX®, an algorithm that has been developed to calculate an individual's ten-year fracture risk. However, only little, or conflicting data is available on a possible association between smoking dose, duration, length of time after cessation, type of tobacco and fracture risk, limiting this risk factor's applicability in the context of FRAX®.

Testostérone et os: indications et limites [Testosterone and bone: indications and limitations].

Osteoporosis incidence increases exponentially with age in men and hypogonadism represents a risk factor. Sex steroids levels are correlated to bone mineral density and to fracture prevalence. Most studies demonstrate an improvement in bone mineral density in men with hypogonadism as a result of testosterone therapy. Nevertheless there are no data evaluating the effect of testosterone therapy on fractures in men. Approximately 20% of men older than 60 have a total testosterone level lower than the lower limit of the reference range but there is no true consensus on the definition of hypogonadism in older men. In older men we recommend to treat only if total morning testosterone levels are < 8 nmol/l or even < 6,9 nmol/l on several occasions in the absence of any reversible illness and if there is no contraindication for treatment.

Joint Official Positions of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX(®). Executive Summary of the 2010 Position Development Conference on Interpretation and use of FRAX® in clinical practice.

The International Society for Clinical Densitometry (ISCD) and the International Osteoporosis Foundation (IOF) convened the FRAX(®) Position Development Conference (PDC) in Bucharest, Romania, on November 14, 2010, following a two-day joint meeting of the ISCD and IOF on the "Interpretation and Use of FRAX(®) in Clinical Practice." These three days of critical discussion and debate, led by a panel of international experts from the ISCD, IOF and dedicated task forces, have clarified a number of important issues pertaining to the interpretation and implementation of FRAX(®) in clinical practice. The Official Positions resulting from the PDC are intended to enhance the quality and clinical utility of fracture risk assessment worldwide. Since the field of skeletal assessment is still evolving rapidly, some clinically important issues addressed at the PDCs are not associated with robust medical evidence. Accordingly, some Official Positions are based largely on expert opinion. Despite limitations inherent in such a process, the ISCD and IOF believe it is important to provide clinicians and technologists with the best distillation of current knowledge in the discipline of bone densitometry and provide an important focus for the scientific community to consider. This report describes the methodology and results of the ISCD-IOF PDC dedicated to FRAX(®).

FRAX(®) Bone Mineral Density Task Force of the 2010 Joint International Society for Clinical Densitometry International Osteoporosis Foundation Position Development Conference.

FRAX(®) is a fracture risk assessment algorithm developed by the World Health Organization in cooperation with other medical organizations and societies. Using easily available clinical information and femoral neck bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA), when available, FRAX(®) is used to predict the 10-year probability of hip fracture and major osteoporotic fracture. These values may be included in country specific guidelines to aid clinicians in determining when fracture risk is sufficiently high that the patient is likely to benefit from pharmacological therapy to reduce that risk. Since the introduction of FRAX(®) into clinical practice, many practical clinical questions have arisen regarding its use. To address such questions, the International Society for Clinical Densitometry (ISCD) and International Osteoporosis Foundations (IOF) assigned task forces to review the best available medical evidence and make recommendations for optimal use of FRAX(®) in clinical practice. Questions were identified and divided into three general categories. A task force was assigned to investigating the medical evidence in each category and developing clinically useful recommendations. The BMD Task Force addressed issues that included the potential use of skeletal sites other than the femoral neck, the use of technologies other than DXA, and the deletion or addition of clinical data for FRAX(®) input. The evidence and recommendations were presented to a panel of experts at the ISCD-IOF FRAX(®) Position Development Conference, resulting in the development of ISCD-IOF Official Positions addressing FRAX(®)-related issues.

Official Positions for FRAX® clinical regarding biochemical markers from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX®.

The best indirect evidence that increased bone turnover contributes to fracture risk is the fact that most of the proven therapies for osteoporosis are inhibitors of bone turnover. The evidence base that we can use biochemical markers of bone turnover in the assessment of fracture risk is somewhat less convincing. This relates to natural variability in the markers, problems with the assays, disparity in the statistical analyses of relevant studies and the independence of their contribution to fracture risk. More research is clearly required to address these deficiencies before biochemical markers might contribute a useful independent risk factor for inclusion in FRAX(®).